How does GPCR interaction alter calcium channels modulation?

CORDISCO GONZALEZ S.; GARCÍA MELANO A.; MUSTAFÁ E.R.; BORTOLOTTO E.; RAINGO J.; MCCARTHY C. I.; RODRIGUEZ S. S.

Congreso; XXXV ANNUAL MEETING SAN 2020; 2020

Sociedad Argentina de Investigación en Neurociencias

Several G protein-coupled receptors (GPCR) are able to form homo or heteromers. Currently, there is an increasing amount of information about dramatic changes in the GPCR activity level and signaling cascades when receptor-receptor interaction occurs. Our laboratory is dedicated to understand the impact of voltage-gated calcium channel (CaV) regulation in neuronal function. We have studied the role of GPCR-mediated modulation of several CaV subtypes. Our current aim is to uncover the dramatic changes in this modulation due to hetero and homomerization of GPCRs. Here, we will present several pieces of evidence suggesting that dopamine receptor type 2 (D2R) and ghrelin receptor (GHSR) heteromers, D1R and GHSR heteromers, GHSR homodimers and D1R homodimers have a unique effect on calcium channels activity. Using different experimental approaches, we investigate the effect of GPCR dimerization on their agonist-dependent activity as well as the basal effect due to constitutive activity of the GPCR. In this line we test compounds with reported activity of inverse agonist to block or reduce the GPCRs interaction and/or their constitutive activity.